Expression and Regulation of Toll-Like Receptor 2 in Rheumatoid Arthritis Synovium
| Autor: | Reinhart Seibl, Thomas Birchler, Susanne Loeliger, Johann Peter Hossle, Renate E. Gay, Traudl Saurenmann, Beat A. Michel, Reinhard A. Seger, Steffen Gay, Roger P. Lauener |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
musculoskeletal diseases
T-Lymphocytes Arthritis Receptors Cell Surface Biology Pathology and Forensic Medicine Arthritis Rheumatoid Reference Values Osteoarthritis medicine Drosophila Proteins Humans DNA Primers Regulation of gene expression Toll-like receptor Membrane Glycoproteins Base Sequence Reverse Transcriptase Polymerase Chain Reaction Macrophages Synovial Membrane Toll-Like Receptors RNA Probes Fibroblasts medicine.disease Immunohistochemistry Toll-Like Receptor 2 TLR2 medicine.anatomical_structure Gene Expression Regulation Immunology Cancer research Tumor necrosis factor alpha Signal transduction Synovial membrane Cell activation Regular Articles |
| Popis: | Toll-like receptors (TLRs) are involved in mediating cell activation on stimulation with microbial constituents. We investigated the role for TLRs in synovial fibroblast (SF) activation in rheumatoid arthritis (RA). We analyzed whether stimulation with interleukin-1 beta and tumor necrosis factor-alpha, cytokines present in RA synovium, influences expression of TLR genes in SFs. The effects were compared with those of treatment with lipopolysaccharide and a synthetic lipopeptide (sBLP). Gene expression was examined using quantitative polymerase chain reaction. TLR2-mediated cell activation was investigated by electromobility shift assay for nuclear factor-kappa B. To localize TLR2 expression in joint tissue sections of RA patients were stained using in situ hybridization. Expression of TLR2 in RA SFs was increased after treatment with interleukin-1 beta, tumor necrosis factor-alpha, lipopolysaccharide, and sBLP. Nuclear factor-kappa B translocation in SFs was triggered by TLR2-mediated cell stimulation. Synovial tissues from RA joints expressed TLR2 predominantly at sites of attachment and invasion into cartilage and bone. The observed elevated expression of TLR2 in RA SFs could be a consequence of direct exposure to microbial compounds or of the presence of inflammatory mediators in the joint. TLR-associated signaling pathways may contribute to the pathogenesis of RA, either by initiating or perpetuating activation of SFs. |
| Databáze: | OpenAIRE |
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